The rising rates of HPV-positive oropharyngeal cancers in the United States (US) and worldwide are a significant public health concern. In the US, it is estimated that 47% (~65 million) of adults aged e30 years have periodontal disease. This is of concern as studies suggest that chronic periodontitis is associated with systemic health conditions, including oral cancers. Research evaluating the role of local oral factors on natural history of oral HPV is lacking, critical information to develop effective prevention strategies. Given the scarcity of research evaluating the role of chronic oral inflammation on the natural history of oral HPV infection, assessment of the prevalence, genotypes, and correlates of oral HPV infection in the general population is a step toward a better understanding of the burden of this infection and its potential role with oral malignancies. The present cross-sectional study will capitalize on the already established infrastructure of the Study of Overweight Adults Longitudinal Study (SOALS), an ongoing NIH-funded cohort of 1,214 Hispanic adults aged 40-65 years living in the San Juan metropolitan area of Puerto Rico, to design and implement a cross-sectional study to start addressing the gaps described. Specifically, we propose to select a random subsample of 600 non-institutionalized adults who participate in SOALS to assess the prevalence and type distribution of oral HPV infection (overall, high-risk and concurrent multiple-type) in adults with and without periodontal disease, and to assess the association between HPV infection and periodontal disease severity. For the current study, assessment of both periodontal disease and oral HPV testing will be performed using validated NHANES methodology. Measures of risk factors for oral HPV infection will be collected using the audio computer-assisted self-interview (ACASI) methodology, a useful tool for collecting sensitive risk behavioral data. Data on dental assessment, selected sociodemographic characteristics, body mass index, lifestyles, medical and dental histories, and biochemical testing will be obtained from the parent study. For HPV typing, PCR products will be typed by dot-blot hybridization using 38 type-specific probes and two separate mixtures, including oncogenic and non-oncogenic HPV types. To our knowledge, this is the first study that will assess the frequency of oral HPV infection in Hispanic adults with and without periodontal disease. The selected study population will provide us with a unique high-risk group where both periodontal disease and oral HPV infection would be higher. Hence, we can study this association with high efficiency and at a reasonable cost. If longitudinal studies in cancer-free individuals confirm that periodontal disease increases the risk of oral HPV infection, preventive public health strategies could be developed, as periodontal disease screening could identify individuals at increased risk of oral HPV infection and oral cancer, particularly among minority, low-income, and underserved populations where oral health disparities are prevalent.